title: Involvement of intercellular adhesion molecule-1 in the antigen-induced infiltration of eosinophils and lymphocytes into the airways in a murine model of pulmonary inflammation.
abstract: We investigated the effects of in vivo intraperitoneal treatment with the rat monoclonal antibody (mAb), YN1.7.4 (YN1) against intercellular adhesion molecule-1 (ICAM-1) on the ovalbumin (OA)-inhalation-induced infiltration of leukocytes into the airways of OA-sensitized mice. YN1 (100 to 400 microg) given over a period of 72 h dose-dependently reduced the influx of lymphocytes and eosinophils into the bronchial lumen by > 60% and > or = 70%, respectively, when compared with saline or purified rat IgG-treated controls. Alveolar macrophages (AM) in the bronchoalveolar lavage fluid (BALF) were also decreased by > 50%. Lung tissue inflammation as determined by histopathologic examination was reduced. The number of neutrophils in the blood of OA-sensitized mice 3 days after challenge was significantly increased by treatment with YN1. However, at 24 h and 72 h after OA-challenge, the numbers of eosinophils and mononuclear cells in the bone marrow were reduced by YN1 treatment. Additionally, at 72 h after OA-challenge, the numbers of bone-marrow neutrophils were depressed. BALF levels of interleukin-5 (IL-5) and of IgA were lower for YN1-treated mice than for controls. With increasing doses of YN1, the levels of anti-ICAM-1 mAb in the plasma were proportionally increased. To correlate these results with YN1 treatment, blood and BALF T cells and BALF eosinophils were examined with flow cytometry. Blood T cells from YN1-treated mice were unable to bind phycoerythrin (PE)-labeled anti-ICAM- mAb ex vivo. These results implied that ICAM-1 on these cells was bound (occupied) by YN1 administered in vivo. Dose-related decreases were observed in the percentage and mean channel fluorescence (MCF) values of ICAM-1+ BALF T cells and eosinophils. The percentages of CD11a+ or CD49d+ eosinophils were also suppressed. Our data suggest that ICAM-1 is an important molecule involved in the recruitment of leukocytes into the airways of sensitized mice after pulmonary challenge.
authors.affiliation: Cell Biology and Inflammation Research, and Drug Development Toxicology, Pharmacia and Upjohn Inc., Kalamazoo, Michigan 49001, USA. jechin@am.pnu.com
authors.forename: J E
authors.initials: JE
authors.lastname: Chin
authors.forename: G E
authors.initials: GE
authors.lastname: Winterrowd
authors.forename: C A
authors.initials: CA
authors.lastname: Hatfield
authors.forename: J R
authors.initials: JR
authors.lastname: Brashler
authors.forename: R L
authors.initials: RL
authors.lastname: Griffin
authors.forename: S L
authors.initials: SL
authors.lastname: Vonderfecht
authors.forename: K P
authors.initials: KP
authors.lastname: Kolbasa
authors.forename: S F
authors.initials: SF
authors.lastname: Fidler
authors.forename: K L
authors.initials: KL
authors.lastname: Shull
authors.forename: R F
authors.initials: RF
authors.lastname: Krzesicki
authors.forename: K A
authors.initials: KA
authors.lastname: Ready
authors.forename: C J
authors.initials: CJ
authors.lastname: Dunn
authors.forename: L M
authors.initials: LM
authors.lastname: Sly
authors.forename: N D
authors.initials: ND
authors.lastname: Staite
authors.forename: I M
authors.initials: IM
authors.lastname: Richards
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D000941:Antigens / Q000276:immunology; D001854:Bone Marrow Cells; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D015848:Interleukin-5 / Q000032:analysis; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D007070:Immunoglobulin A; D015848:Interleukin-5; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin